1. Dendritic cells fused with core binding factor-beta positive acute myeloid leukaemia blast cells induce activation of cytotoxic lymphocytes
- Author
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Marianne Hoeck, Nurguel Usluoglu, Hans Pralle, G.-Andre Banat, Kerstin Ihlow, and Sabine Hoppmann
- Subjects
CD40 ,biology ,Hematology ,Dendritic cell ,T lymphocyte ,Major histocompatibility complex ,hemic and lymphatic diseases ,MHC class I ,Immunology ,biology.protein ,Cancer research ,Cytotoxic T cell ,Antigen-presenting cell ,CD8 - Abstract
Summary Several reports have described various strategies of dendritic cell (DC) vaccination to induce specific T-cell responses in patients with acute myeloid leukaemia (AML). About 50–60% of AML cases blasts have chromosomal abnormalities, such as inv(16) or t(8,21), which could encode for leukaemia-specific antigenic peptide sequences, possibly presented in the context of self-major histocompatibility complex (MHC) molecules. As the co-culture of AML blasts with T lymphocytes seldom resulted in T-cell stimulation, we fused AML blasts with autologous DC to enhance this effect. The fusion cells expressed MHC class I and II, CD40, B7-1, B7-2, CD209 and several adhesion molecules. In a mixed lymphocyte hybrid reaction, the fusion cells induced the proliferation of autologous T cells. Moreover, in the special case of fusion cells established from AML blasts with the chromosomal abnormality inv(16), the autologous T lymphocytes could be primed to induce cytotoxicity against up to 70% autologous AML blasts in a effector:target ratio of 20:1. Blocking assays demonstrated that the lysis was chiefly mediated by CD8+, CCR7− T lymphocytes, which could be further expanded in the form of effector memory CD8+ T cells by repeated co-cultures with the autologous fusion cells.
- Published
- 2004
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